Ruthenium-based catalytic complexes and the use of such complexes for olefin metathesis

ABSTRACT

Disclosed herein are compounds of the formula (I) or (II) in which: L is a neutral ligand; X, X′ are anionic ligands; R 1  and R 2  are, separately, a hydrogen, a C 1 -C 6  alkyl, a C 1 -C 6  perhalogenoalkyl, a aldehyde, a ketone, an ester, a nitrile, an aryl, a pyridinium alkyl, an optionally substituted C 5  or C 6  pyridinium alkyl, perhalogenoalkyl or cyclohexyl, a C n h2 N Y radical 10 with n between 1 and 6 and y an iconic marker, or a radical having the formula: wherein R 1  can be a radical of formula (Ibis) when the compound has formula (I) or of formula (IIbis) when the compound has formula (II), R 3  is a C 1 -C 6  alkyl, or a C 5  or C 6  cycloalkyl or a C 5  or C 6  aryl; R 0 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , are, separately, a hydrogen, C 1 -C 6  alkyl, a C 1 -C 6  perhalogenoalkyl, or a C 5  or C 6  aryl; wherein R 9 , R 10 , R 11  can be a heterocycle; X 1  is anion. R 1  and R 2  can form, with the N and the C to which they are attached, a heterocycle.

INTRODUCTION AND BACKGROUND

This invention relates to new activated and recyclable ruthenium-basedcatalytic complexes as well as a method for synthesis of same.

The invention also relates to the use of such catalytic complexes forolefin metathesis.

The development of recyclable or activated ruthenium-based catalyticcomplexes is based on the work of R. Grubbs of the University ofCalifornia (USA) relating to the ruthenium complex 2a (precatalyst 2b)called the Grubbs II catalyst.

Thus, the first recyclable complex 3a (precatalyst 3b) with a styrenylether ligand (called a “boomerang” ligand) was described by Hoveyda ofthe University of Boston (USA).

This compound is described in particular in the international patentapplication WO 0214376.

A first advantage of this complex is that it enables recycling of theprecatalyst, which is recovered at the end of the reaction and can bereused.

However, this catalyst has the disadvantage of leading to significantlosses, in an amount of 10% per cycle.

A second advantage of this complex is that it minimizes the presence oftoxic metal residue (ruthenium) in the reaction products.

However, this complex is less active than the Grubbs 2b complexdescribed above.

The first activated complex 4 was described in 2002, based on theelectronic effect produced by the presence of a nitro group (NO₂) on theHoveyda styrenyl ether ligand described above.

This activated complex is described in the international patentapplication WO 2004 035596.

The activation of this precatalyst is based on the significantlyaccelerated detachment of the styrenyl ether ligand, which causes arapid initiation of the catalytic cycle and therefore a significantincrease in the reaction kinetics. The reactions can then take placeunder gentler conditions, in practice at room temperature, and withlower catalytic loads.

However, this complex is not easily recycled, and thus leads tosignificant toxic metal residue (ruthenium) contamination in thereaction products. Such a disadvantage is particularly detrimental tothe synthesis of certain high added value products such aspharmaceutical molecules.

According to the prior art, it therefore appears that reactivity andrecycling of such ruthenium complexes are two antinomic propertiessince, in practice, the increase in the activity is achieved at theexpense of the recycling, and, conversely, the increase in recycling isachieved at the expense of the reactivity of the catalytic species.

SUMMARY OF THE INVENTION

The objective of this invention is to describe activated and recyclableruthenium complexes in which the compromise between these antinomicproperties can be optimized, i.e. complexes capable of having anexcellent activity while preserving good recycling.

An objective of this invention is therefore to propose such complexeswhich use can enable a decrease in the catalytic load. Such an objectiveis important in consideration of the high cost of these catalysts.

An objective of this invention is therefore to propose such complexeswhich degree of recyclability leads to a significant reduction in thetoxic metal waste in the end products.

In the best of cases, the catalysts according to this invention willenable products to be obtained with a very low ruthenium content, inpractice below 10 to 20 ppm.

These objectives are achieved by the invention, which relates to anycompound of formula (I) or (II):

in which:

L is a neutral ligand;

X, X′ are anionic ligands;

R¹ and R² are, independently, an hydrogen, a C₁ to C₆ alkyl, a C₁ to C₆perhalogenoalkyl, an aldehyde, a ketone, an ester, an amide, a nitrile,an optionally substituted aryl, a pyridinium alkyl, a pyridiniumperhalogenoalkyl or an optionally substituted C₅ or C₆ cyclohexyl, aC_(n)H_(2n)Y or C_(n)F_(2n)Y radical with n being between 1 and 6 and Ybeing an ion marker, or a radical of formula:

R¹ can be a radical of formula (Ibis) when the compound is of formula I:

or of formula (II bis) when the compound is of formula (II):

R³ is a C₁ to C₆ alkyl or a C₅ or C₆ cycloloalkyl or a C₅ or C₆ aryl;

R⁰, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹ are, independently, an hydrogen, aC₁ to C₆ alkyl, a C₁ to C₆ perhalogenoalkyl, or a C₅ or C₆ aryl; R⁹,R¹⁰, R¹¹ can form a heterocycle;

X¹ is an anion: halogen, tetrafluoroborate ([BF₄]⁻),[tetrakis-(3,5-bis-(trifluoromethyl)-phenyl)borate] ([BARF]⁻),hexafluorophosphate ([PF₆]⁻), hexafluoroantimoine ([SbF₆]⁻),hexafluoroarsenate ([AsF₆]⁻), trifluoromethylsulfonate ([(CF₃)₂N]⁻);

R¹ and R² can form with the N and the C to which they are attached aheterocycle of formula:

wherein hal is an halogen and R¹² is an hydrogen, a C₁ to C₆ alkyl, or aC₅ or C₆ cycloalkyl or a C₅ or C₆ aryl.

Preferably, L is P(R¹³)₃, with R¹³ being a C₁ to C₆ alkyl or an aryl ora C₅ or C₆ cycloalkyl.

Also preferably, L is a ligand of formula 7a, 7b, 7c, 7d or 7e:

in which: n¹=0, 1, 2, 3;

R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸, R¹⁹, R²⁰, R²¹, R²², R²³, R²⁴, R²⁵, R²⁶, R²⁷,R²⁸ are independently a C₁ to C₆ alkyl, a C₃ to C₂₀ cycloalkyl, a C₂ toC₂₀ alkenyl, a naphthyl, an anthracene or a phenyl, wherein said phenylcan be substituted by up to 5 groups chosen from the C₁ to C₆ alkyls,the C₁ to C₆ alkoxys and the halogens; R¹⁶ and R¹⁷, and R²⁶ and R²⁷ canform a cycle with 3, 4, 5, 6, or 7 links; R²⁶ can independently form anaromatic cycle with 6 conjoined links.

Advantageously, L is PCy₃, with Cy being cyclohexyl, or L is a ligand offormula 7a or 7b. X is a chlorine, and X′ is a chlorine.

The ion marker Y is preferably chosen from the group consisting of:

According to an alternative, the compound according to the inventionsatisfies formula (I) in which R¹ is chosen from the group consisting ofCH₃, CF₃, C₆F₅, pNO₃C₆H₄.

According to an alternative, the compound satisfies formula 1a:

According to another alternative, the compound satisfies formula 1b:

According to another alternative, the compound satisfies formula 1c:

According to another alternative, the compound satisfies formula 1d:

According to another alternative, the compound satisfies formula 1e:

According to another alternative, the compound satisfies formula 1f:

According to another alternative, the compound satisfies formula 1g:

According to another alternative, the compound satisfies formula 1h:

According to another alternative, the compound satisfies formula 1i:

According to another alternative, the compound satisfies formula 1j:

According to another alternative, the compound satisfies formula 1k:

According to another alternative, the compound satisfies formula 11:

According to another alternative, the compound satisfies formula 12:

According to another alternative, the compound satisfies formula 13:

According to another alternative, the compound satisfies formula 14:

The invention also relates to any method for the synthesis of a compoundof formula (I) characterized in that it includes a first step consistingof reacting 4-isopropoxy-3-vinylaniline with a compound having an acylfunction so as to obtain an amide ligand and a second step consisting ofreacting said amide ligand with a compound of formula (III):

Preferably, said compound of formula (III) is the Grubbs precatalyst(2b) or the Nolan precatalyst (2c).

The introduction, according to the invention, of an amide function onthe styrenyl ether ligand has the specially promotes the activation ofthe catalyst.

In particular, when the amide function has a perfluorinated methyl(trifluoromethyl), a significant activation of the catalyst is observedand is characterized by relatively high conversions in very shortamounts of time. Under these conditions, an economic impact can beenvisaged by significantly reducing the catalytic load in the metathesisreactions without affecting the yield.

In addition, this amide function can act as a spacer for theintroduction of an ion marker (“tag”) for immobilization in the aqueousand/or ion phase as well as on a solid support.

Such an ion marking enables better recycling of the catalytic complexesto be performed in aqueous/ion solvents or on a solid support(continuous flow reaction) and enables a clear reduction in the cost ofthe reaction while avoiding contamination of high added value products,in particular in the context of a pharmaceutical molecule synthesisprocess.

The invention, as well as the various advantages thereof, will be easierto understand in view of the following description of various examplesof embodiments thereof provided in reference to the figures.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph showing the conversion rate over time of ametallyl-allyl diethyl malonate compound in the context of a metathesiscyclization reaction at room temperature, in the presence of 1 mol % ofthe Hoveyda complex 3b on one hand and in the presence of 1 mol % ofcatalytic complexes according to the invention 1a, 1b, 1c and 1d on theother hand;

FIG. 2 is a graph showing the conversion rate over time of ametallyl-allyl diethyl malonate compound in the context of a metathesiscyclization reaction at room temperature, in the presence of 1 mol % ofthe Hoveyda complex 3b on one hand and in the presence of 1 mol % ofcatalytic complexes according to the invention 1b and 1e on the otherhand;

FIG. 3 is a graph showing the conversion rate over time of ametallyl-allyl diethyl malonate compound in the context of a metathesiscyclization reaction at 45° C., in the presence of 1 mol % of thecatalytic complex according to the invention 1e;

FIG. 4 is a graph showing the conversion rate over time of ametallyl-allyl diethyl malonate compound in the context of a metathesiscyclization reaction at 30° C., in the presence of 1 mol % of thecatalytic complex according to the invention 1b on one hand and in thepresence of 0.3 mol % of the catalytic complex according to theinvention 1b on the other hand;

FIG. 5 is a graph showing the conversion rate over time of ametallyl-allyl diethyl malonate compound in the context of a metathesiscyclization reaction at 30° C., in the presence of 1 mol % of thecatalytic complex according to the invention 1b, 1e and 1f;

FIGS. 6 to 11 show the NMR spectra of various examples of rutheniumcomplexes 1a, 1b, 1c, 1d, 1e and 1f.

LEGEND

FIGS. 1 through 5

conversion conversion temps time

DETAILED DESCRIPTION OF INVENTION

First, the synthesis of the various examples of complexes according tothe invention will be described below.

The complexes 1a, 1b, 1c, 1d, 1e and 1f according to the invention areobtained in two steps from the functionalized aniline 5.

The 4-step method of synthesis of this functionalized aniline 5 frompara-nitro-phenol is described in the article “Activatedpyridinium-tagged ruthenium complex as efficient catalyst forRing-Closing Metathesis.” D. Rix, H. Clavier, Y. Coutard, L. Gulajski,K. Grêla*, M. Mauduit*, J. Organomet. Chem., 2006, 691, 5397-5405.

The following diagram summarizes this synthesis in two steps:

1^(st) step: synthesis of amides 6a, 6b, 6c, 6d, 6f, 9a, 9b, 10a and 10bfrom 4-isopropoxy-3-vinylaniline 5

According to a general procedure, 4-isopropoxy-3-vinylaniline 5 (1 eq.;around 0.2 mmol) is introduced into a round-bottom flask, placed undernitrogen, and solubilized in anhydrous dichloromethane (2-3 mL).Pyridine (1.5 eq.) is added to the solution, which is then cooled to 0°C. Acyl chloride or anhydride (1.2 eq) is then slowly added, then thereaction medium is agitated at room temperature under nitrogen for 2hours.

The raw material is then diluted with dichloromethane (10 mL), washedwith an aqueous hydrochloric acid solution 1N (2 mL), then with asaturated sodium hydrogen carbonate solution (2×2 mL) and finally with asaturated sodium chloride solution (3×2 mL). The organic phases arecollected, dried on magnesium sulfate and concentrated under vacuum.

The residue is purified by chromatography on silica gel.

Synthesis of the N-(4-isopropoxy-3-vinylphenyl)acetamide compound 6a

Using the general procedure for obtaining amides from4-isopropoxy-3-vinylaniline 5 (50 mg; 0.3 mmol) and with acetyl chloride(15 μL), acetamide is obtained after chromatography on silica gel(eluent: CH₂Cl₂/AcOEt (4:1)) in the form of a pink solid (49 mg, 78%).

Rf (CH₂Cl₂/AcOEt (4:1))=0.48

NMR ¹H (400 MHz, CDCl₃) δ (ppm): 7.54 (s, 1H, NH); 7.51 (d, 1H, ⁴J=2.7Hz, H₇); 7.38 (dd, 1H, ³J=8.8 Hz, ⁴J=2.7 Hz, H₅); 6.99 (dd, 1H,³J_(cis)=11.2 Hz, ³J_(trans)=17.8 Hz, H₉); 6.81 (d, 1H, ³J=8.8 Hz, H₄);5.68 (dd, 1H, ²J_(gem)=1.4 Hz, ³J_(trans)=17.8 Hz, H_(10a)); 5.22 (dd,1H, ²J_(gem)=1.4 Hz, ³J_(cis)=11.2 Hz, H_(10b)); 4.45 (sept., 1H, ³J=6.1Hz, H₂); 2.14 (s, 3H, H₁₁); 1.31 (d, 6H, ³J=6.1 Hz, H₁)

NMR ¹³C (100 MHz, CDCl₃) δ (ppm): 168.4 (C═O); 152.0 (C3); 131.4 (C9);131.1 (C8); 128.3 (C6); 121.2 (C7); 118.6 (C5); 115.1 (C4); 114.5 (ClO);71.4 (C2); 24.3 (C1l); 22.1 (Cl).

Synthesis of the N-(4-isopropoxy-3-vinylphenyl)trifluoroacetamidecompound 6b

Using the general procedure for obtaining amides from4-isopropoxy-3-vinylaniline 5 (26 mg; 0.14 mmol) and withtrifluoroacetic anhydride (25 μL), trifluoroacetamide is obtained afterchromatography on silica gel (eluent: CH₂Cl₂/EP (9:1)) in the form of ayellowish solid (23 mg, 59%).

Rf (CH₂Cl₂/EP (9:1))=0.65

NMR ¹H (400 MHz, CDCl₃) δ (ppm): 7.93 (s, 1H, NH); 7.59 (d, 1H, ⁴J=2.7Hz, H₇); 7.44 (dd, 1H, ³J=8.9 Hz, ⁴J=2.7 Hz, H₅); 7.01 (dd, 1H,³J_(cis)=11.2 Hz, ³J_(trans)=17.8 Hz, H₉); 6.88 (d, 1H, ³J=8.9 Hz, H₄);5.74 (dd, 1H, ²J_(gem)=1.3 Hz, ³J_(trans)=17.9 Hz, H_(10a)); 5.28 (dd,1H, ²J_(gem)=1.3 Hz, ³J_(cis)=11.2 Hz, H_(10b)); 4.53 (sept., 1H, ³J=6.1Hz, H₂); 1.35 (d, 6H, ³J=6.1 Hz, H₁)

NMR ¹⁹F (376.5 MHz, CDCl₃) δ (ppm): −76.1 (s, 3F, F₁₄)

NMR ¹³C (100 MHz, CDCl₃) δ (ppm): 155.7 (quad., ²J_(C-F)=37 Hz, C═O);153.3 (C3); 131.0 (C9); 128.7 (C8); 127.9 (C6); 121.2 (C7); 119.0 (C5);115.8 (quad., ¹J_(C-F)=288 Hz, C1l); 115.3 (C4); 114.7 (C10); 71.3 (C2);22.1 (C1)

Synthesis of the N-(4-isopropoxy-3-vinylphenyl)pentafluorobenzamidecompound 6c

Using the general procedure for obtaining amides from4-isopropoxy-3-vinylaniline 5 (39 mg; 0.22 mmol) and withpentafluorobenzoyl chloride (38 μL), pentafluorobenzamide is obtainedafter chromatography on silica gel (eluent: CH₂Cl₂/EP (9:1)) in the formof a pink solid (75 mg, 92%).

Rf (CH₂Cl₂/EP (9:1))=0.71

NMR ¹H (400 MHz, CDCl₃) δ (ppm): 7.70 (5, 1H, NH); 7.59 (d, 1H, ⁴J=2.7Hz, H₇); 7.46 (dd, 1H, ³J=8.9 Hz, ⁴J=2.7 Hz, H₅); 7.02 (dd, 1H,³J_(cis)=11.2 Hz, ³J_(trans)=17.8 Hz, H₉); 6.87 (d, 1H, ³J=8.9 Hz, H₄);5.73 (dd, 1H, ²J_(gem)=1.3 Hz, ³J_(trans)=17.9 Hz, H_(10a)); 5.27 (dd,1H, ²J_(gem)=1.3 Hz, ³J_(cis)=11.2 Hz, H_(10b)); 4.52 (sept., 1H, ³J=6.1Hz, H₂); 1.35 (d, 6H, ³J=6.1 Hz, H₁)

NMR ¹⁹F (376.5 MHz, CDCl₃) δ(ppm): −140.5 (d, 2F, ³J_(F·F)=16 Hz, F₇₂);−150.5 (t, 1F, ³J_(F·F)=20 Hz, F₁₄); −160.1 (dt, 2F, ³J_(F·F)=20 Hz,³J_(F·F)=15 Hz, F₁₃)

NMR ¹³C (100 MHz, CDCl₃) δ (ppm): 155.2 (C═O); 152.9 (C3);145.5-142.9-138.9-136.4 (C12, C13, C14); 131.1 (C9); 129.6 (C8); 128.6(C6); 121.2 (C7); 119.0 (C5); 115.1 (C4); 114.8 (C10); 111.6 (C11); 71.4(C2); 22.1 (Cl)

Synthesis of the N-(4-isopropoxy-3-vinylphenyl)/)paranitrobenzamidecompound 6d

Using the general procedure for obtaining amides from4-isopropoxy-3-vinylaniline 5 (38 mg; 0.22 mmol) and withparanitrobenzoyl chloride (48 mg), paranitrobenzamide is obtained afterchromatography on silica gel (eluent: CH₂Cl₂) in the form of a yellowoil (67 mg, 96%).

Rf (CH₂Cl₂)=0.43

NMR ¹H (400 MHz, CDCl₃) δ (ppm): 8.44 (s, 1H, NH); 8.17 (d, 2H, ³J=8.8Hz, H₁₂); 7.96 (d, 2H, ³J=8.8 Hz, H₁₃); 7.61 (d, 1H, ⁴J=2.5 Hz, H₇);7.45 (dd, 1H, ³J=8.8 Hz, ⁴J=2.5 Hz, H₅); 6.97 (dd, 1H, ³J_(cis)=11.2 Hz,³J_(trans)=17.8 Hz, H₉); 6.80 (d, 1H, ³J=8.8 Hz, H₄); 5.63 (dd, 1H,²J_(gem)=1.3 Hz, 3J_(trans)=17.7 Hz, H_(10a)); 5.20 (dd, 1H,²J_(gem)=1.3 Hz, ³J_(cis)=11.1 Hz, H_(10b)); 4.48 (sept., 1H, ³J=6.1 Hz,H₂); 1.33 (d, 6H, ³J=6.1 Hz, H₁)

NMR ¹³C (100 MHz, CDCl₃) δ (ppm): 164.0 (C═O); 152.7 (C3); 149.4 (C14);140.3 (C11); 131.2 (C9); 130.1 (C8); 128.3 (C6); 128.2 (C12); 123.7(C13); 121.8 (C7); 119.4 (C5); 114.7 (C4); 114.6 (C10); 71.2 (C2); 22.0(Cl)

Synthesis of the N,N′-bis(4-isopropoxy-3-vinylphenyl)oxamide compound 6f

4-isopropoxy-3-vinylaniline 5 (30m; 1 eq.; 0.2 mmol) is introduced intoa round-bottom flask, placed under nitrogen, and solubilized inanhydrous dichloromethane (3 mL). Pyridine (21 μL, 1.5 eq.) is added tothe solution, which is then cooled to 0° C. Oxalyl chloride (8.8 μL; 1.2eq.) is then slowly added, then the reaction medium is agitated at roomtemperature under nitrogen for 2 hours.

The raw material is diluted with dichloromethane (10 mL), washed with anaqueous solution of hydrochloric acid 1N (2 mL) then with a saturatedsodium hydrogen carbonate solution (2×2 mL) and finally with a saturatedsodium chloride solution (3×2 mL). The organic phases are collected,dried on magnesium sulfate and concentrated under vacuum.

The residue is purified by chromatography on silica gel (eluent:CH₂Cl₂/EP (9:1)) to produce the desired compound 6f in the form of awhite solid (14 mg, 20%).

Rf (CH₂Cl₂/EP (9:1))=0.66

NMR ¹H (400 MHz, CDCl₃) δ (ppm): 9.30 (s, 2H, NH); 7.75 (d, 2H, ⁴J=2.7Hz, H₇); 7.55 (dd, 2H, ³J=8.9 Hz, ⁴J=2.7 Hz, H₅); 7.04 (dd, 2H,³J_(cis)=11.2 Hz, ³J_(trans)=17.8 Hz, H₉); 6.89 (d, 2H, ³J=8.9 Hz, H₄);5.76 (dd, 2H, ²J_(gem)=1.3 Hz, ³J_(trans)=17.9 Hz, H_(10a)); 5.29 (dd,2H, ²J_(gem)=1.3 Hz, ³J_(cis)=11.2 Hz, H_(10b)); 4.53 (sept., 2H, ³J=6.1Hz, H₂); 1.35 (d, 12H, ³J=6.1 Hz, H₁)

NMR ¹³C (100 MHz, CDCl₃) δ (ppm): 157.3 (C═O); 152.8 (C3); 131.2 (C9);129.4 (C8); 128.6 (C6); 120.4 (C7); 118.2 (C5); 115.1 (C4); 114.9 (Cl0);71.3 (C2); 22.1 (Cl)

Synthesis of the N-(4-isopropoxy-3-vinylphenyl)difluorochloroacetamidecompound 9a

Using the general procedure for obtaining amides from4-isopropoxy-3-vinylaniline 5 (50 mg; 0.3 mmol) and with2-chloro-2.2-difluoroethanoic anhydride (63 μL), acetamide is obtainedafter chromatography on silica gel (eluent: CH₂Cl₂/AcOEt (4:1)) in theform of a pink solid (65 mg, 75%).

Rf (CH₂Cl₂/EP (4:1))=0.75

NMR ¹H (400 MHz, CDCl₃) δ (ppm): 7.54 (s, 1H, NH); 7.59 (d, 1H, ⁴J=2.7Hz, H₇); 7.43 (dd, 1H, ³J=8.8 Hz, ⁴J=2.7 Hz, H₅); 6.99 (dd, 1H,³J_(cis)=11.2 Hz, ³J_(trans)=17.8 Hz, H₉); 6.86 (d, 1H, ³J=8.8 Hz, H₄);5.70 (dd, 1H, ²J_(gem)=1.4 Hz, ³J_(trans)=17.8 Hz, H_(10a)); 5.27 (dd,1H, ²J_(gem)=1.4 Hz, ³J_(cis)=11.2 Hz, H_(10b)); 4.50 (sept., 1H, ³J=6.1Hz, H₂); 1.34 (d, 6H, ³J=6.1 Hz, H₁)

NMR ¹⁹F (376.5 MHz, CDCl₃) δ (ppm): −64.3 (s, 2F, CF₂)

NMR ¹³C (100 MHz, CDCl₃) δ (ppm): 158.8 (C═O); 153.2 (C3); 131.0 (C9);128.6 (C8); 128.1 (C6); 122.2 (CF₂Cl); 121.2 (C5); 119.1 (C4); 116.2(CF₂Cl); 114.7 (Cl0); 71.3 (C2); 22.0 (Cl)

Synthesis of the3-{1,1-difluoro-2-[4-isopropoxy-3-vinylphenylamino]-2-oxoethyl}-1-methyl-1H-imidazol-3-iumcompound 9c

Chlorinated amide 9a (20 mg; 0.07 mmol) is solubilized in anhydroustoluene (2.5 mL). N-methylimidazole (1 mL; 20 eq.) is added to thesolution, which is then brought to reflux overnight. The volatile phasesare then removed under reduced pressure and the tagged compound isrecovered in the form of a dark orange oil.

NMR ¹H (400 MHz, CDCl₃) δ (ppm): 9.49 (s, 1H, NH); 7.67 (d, 1H, ⁴J=2.7Hz, H₇); 7.48 (dd, 1H, ³J=8.8 Hz, ⁴J=2.7 Hz, H₅); 7.43 (s, 1H, H₁₁);7.04 (s, 1H, H₁₂); 7.00 (dd, 1H, ³J_(cis)=11.2 Hz, ³J_(trans)=17.8 Hz,H₉); 6.89 (s, 1H, H₁₃); 6.86 (d, 1H, ³J=8.8 Hz, H₄); 5.70 (dd, 1H,²J_(gem)=1.4 Hz, ³J_(trans)=17.8 Hz, H_(10a)); 5.25 (dd, 1H,²J_(gem)=1.4 Hz, ³J_(cis)=11.2 Hz, H_(10b)); 4.52 (sept., 1H, ³J=6.1 Hz,H₂); 3.68 (s, 3H, H₁₄); 1.33 (d, 6H, ³J=6.1 Hz, H₁)

NMR ¹⁹F (376.5 MHz, CDCl₃) δ (ppm): −64.0 (s, 2F, CF₂)

NMR ¹³C (100 MHz, CDCl₃) δ (ppm): 157.2 (C═O); 153.0 (C3); 131.1 (C9,C1l); 128.8 (C8); 128.4 (C6); 121.5 (C5); 119.3 (C4); 119.1 (CF₂); 114.8(C10); 114.6 (C7); 71.3 (C2); 33.3 (C14); 22.0 (Cl)

Synthesis of the 3-chloro-2.2.3.3-tetrafluoro-7V-(4-isopropoxy-3vinylphenyl)propanamide compound 9b

Using the general procedure for obtaining amides from4-isopropoxy-3-vinylaniline 5 (50 mg; 0.3 mmol) and with3-chloro-2.2.3.3-tetrafluoropropanoyl chloride (81 mg), acetamide isobtained after chromatography on silica gel (eluent: CH₂Cl₂/AcOEt (4:1))in the form of a white solid (65 mg, 57%).

Rf (CH₂Cl₂/AcOEt (9:1))=0.3

NMR ¹H (400 MHz, CDCl₃) δ (ppm): 8.00 (s, 1H, NH); 7.62 (d, 1H, ⁴J=2.7Hz, H₇); 7.44 (dd, 1H, ³J=8.8 Hz, 17.8 Hz, H₉); 6.86 (d, 1H, ³J=8.8 Hz,H₄); 5.72 (dd, 1H, ²J_(gem)=1.4 Hz, ³J_(trans)=17.8 Hz, H_(10a)); 5.28(dd, 1H, ²J_(gem)=1.4 Hz, ³J_(cis)=11.2 Hz, H_(10b)); 4.52 (sept., 1H,³J=6.1 Hz, H₂); 1.34 (d, 6H, ³J=6.1 Hz, H₁)

NMR ¹⁹F (376.5 MHz, CDCl₃) δ (ppm): −70.1 (s, 2F, F₁₁); −118.6 (s, 2F,F₁₂)

NMR ¹³C (100 MHz, CDCl₃) δ (ppm): 155.7 (C═O); 153.3 (C3); 130.9 (C9);128.6 (C8); 128.1 (C6); 124.8 (CF₂CO); 121.2 (C5); 119.0 (C4); 115.2(Cl0); 114.2 (C7); 108.1 (CF₂Cl); 71.3 (C2); 22.0 (Cl)

2^(nd) step: synthesis of ruthenium complexes 1a, 1b, 1c, 1d, 1e, 1f, 11and 12 from amides 6a, 6b, 6c, 6d, 6f, 10b

According to a general procedure, the amide ligand (1 eq.), copperchloride (I) (1 eq) and the indenylidene precatalyst (1 eq.) areintroduced into a round-bottom flask under argon. Anhydrousdichloromethane (2-3 mL) is added to it. The reaction medium is thendegassed three times, placed at 30-33° C. under an argon atmosphere andkept under agitation for around 5 hours.

The raw reaction material is then concentrated under vacuum. The residueis combined with acetone (1-2 mL) and filtered on Celite. The filtrateis concentrated under vacuum and the residue is purified bychromatography on silica gel.

Synthesis of the Ruthenium Complex 1a

Using the general procedure for obtaining ruthenium complexes withN-(4-isopropoxy-3-vinylphenyl)acetamide 6a (24 mg; 0.011 mmol), thecomplex 1a is obtained after chromatography on silica gel (eluent:EP/Acetone (1:1)) in the form of a green solid (73 mg; 98%).

Rf (EP/Acetone (1:1))=0.52

NMR ¹H (400 MHz, (CD₃)₂CO) δ (ppm): 16.42 (s, 1H, H₉); 10.23 (s, 1H,NH); 7.78 (d, 1H, ³J=8.6 Hz, H₅); 7.55 (s, 1H, H₇); 7.05 (s, 4H, H₁₂);6.91 (d, 1H, ³J=8.6 Hz, H₄); 4.88 (sept., 1H, ³J=6.1 Hz, H₂); 4.24 (s,4H, H₁₀); 2.45 (m, 18H, H₁₁, H₁₃); 2.09 (s, 3H, H₁₄); 1.22 (d, 6H,³J=6.1 Hz, H₁)

Synthesis of the Ruthenium Complex 1b

Using the general procedure for obtaining ruthenium complexes withN-(4-isopropoxy-3-vinylphenyl)trifluoroacetamide 6b (11.7 mg; 0.04mmol), complex 1b is obtained after chromatography on silica gel(eluent: EP/Acetone (7:3)) in the form of a green solid (26.1 mg; 88%).

Rf (EP/Acetone (3:2))=0.37

NMR ¹⁹F (376.5 MHz, (CD₃)₂CO) δ (ppm): −76.5 (s, 3F, F₁₄)

NMR ¹H (400 MHz, (CD₃)₂CO) δ (ppm): 16.40 (s, 1H, H₉); 9.24 (s, 1H, NH);7.64 (dd, 1H, ³J=8.6 Hz, ⁴J=2.8 Hz, H₅); 7.55 (d, 1H, ⁴J=2.8 Hz, H₇);7.05 (s, 4H, H₁₂); 7.01 (d, 1H, ³J=8.6 Hz, H₄); 4.95 (sept., 1H, ³J=6.1Hz, H₂); 4.27 (s, 4H, H₁₀); 2.43 (m, 18H, H₁₁, H₁₃); 1.22 (d, 6H ³J=6.1Hz, H₁)

Synthesis of the Du Ruthenium Complex 1c

Using the general procedure for obtaining ruthenium complexes withN-(4-isopropoxy-3-vinylphenyl)pentafluorobenzamide 6c (9 mg; 0.02 mmol),complex 1c is obtained after chromatography on silica gel (eluent:EP/Acetone (7:3)) in the form of a green solid (10 mg; 50%).

Rf (EP/Acetone (7:3))=0.41

NMR ¹⁹F (376.5 MHz, (CD₃)₂CO) δ (ppm): −143.6 (d, 2F, ³J_(F·F)=15 Hz,F₁₅); −155.2 (t, 1F, ³J_(F·F)=20 Hz, F₁₇); −16.5 (dt, 2F, ³J_(F·F)=20Hz, ³J_(F·F)=15 Hz, F₁₆)

NMR ¹H (400 MHz, (CD₃)₂CO) δ (ppm): 16.41 (s, 1H, H₉); 10.35 (s, 1H,NH); 7.75 (dd, 1H, ³J=8.6 Hz, ⁴J=2.8 Hz, H₅); 7.67 (d, 1H, ⁴J=2.8 Hz,H₇); 7.07 (s, 4H, H₁₂); 7.03 (d, 1H, ³J=8.6 Hz, H₄); 4.95 (sept., 1H,³J=6.1 Hz, H₂); 4.27 (s, 4H, H₁₀); 2.43 (m, 18H, H₁₁, H₁₃); 1.22 (d, 6H,³J=6.1 Hz, H₁)

Synthesis of the Ruthenium Complex 1d

Using the general procedure for obtaining ruthenium complexes withN-(4-isopropoxy-3-vinylphenyl)/paranitrobenzamide 6d (8 mg; 0.02 mmol),complex 1d is obtained after chromatography on silica gel (eluent:EP/Acetone (6:4)) in the form of a green solid (18 mg; 95%).

Rf (EP/Acetone (7:3))=0.34

NMR ¹H (400 MHz, (CD₃)₂CO) δ (ppm): 16.46 (s, 1H, H₉); 9.97 (s, 1H, NH);8.36 (d, 2H, ³J=8.8 Hz, H₁₅); 8.21 (d, 2H, ³J=8.8 Hz, H₁₆); 7.85 (dd,1H, ³J=8.6 Hz, ⁴J=2.8 Hz, H₅); 7.74 (d, 1H, ⁴J=2.8 Hz, H₇); 7.07 (s, 4H,H₁₂); 7.02 (d, 1H, ³J=8.6 Hz, H₄); 4.95 (sept., 1H, ³J=6.1 Hz, H₂); 4.27(s, 4H, H₁₀); 2.43 (m, 18H, H₁₁, H₁₃); 1.24 (d, 6H, ³J=6.1 Hz, H₁)

Synthesis of the Ruthenium Complex 1e

The N-(4-isopropoxy-3-vinylphenyl)trifluoro-acetamide ligand 6b (22 mg;0.08 mmol; 1 eq.), copper chloride (I) (8 mg, 1 eq) and the 2^(nd)generation Nolan precatalyst (68 mg, 1 eq.) of formula 2c are introducedinto a round-bottom flask under argon. Anhydrous dichloromethane (3 mL)is added to it. The reaction medium is then degassed three times, placedat 30-33° C. under an argon atmosphere and kept under agitation foraround 5 hours.

The raw reaction material is then concentrated under vacuum. The residueis combined with acetone (1-2 mL) and filtered on Celite. The filtrateis concentrated under a vacuum and the residue is purified bychromatography on silica gel.

The complex 1e is obtained after chromatography on silica gel (eluent:EP/Acetone (4:1)) in the form of a green solid (52 mg; 88%). Rf(EP/Acetone (1:1))=0.13

NMR ¹⁹F (376.5 MHz, (CD₃)₂CO) δ (ppm): −76.5 (s, 3F, F₁₄)

NMR ¹H (400 MHz, (CD₃)₂CO) δ (ppm): 16.54 (s, 1H, H₉); 10.44 (s, 1H,NH); 7.79 (dd, 1H, ³J=8.6 Hz, ⁴J=2.6 Hz, H₅); 7.68 (d, 1H, ⁴J=2.6 Hz,H₇); 7.48 (s, 2H, H₁₀); 7.14 (s, 4H, H₁₂); 7.09 (m, 1H, H₄); 4.99(sept., 1H, ³J=6.1 Hz, H₂); 2.47 (s, 6H, H₁₇); 2.24 (s, 12H, H₁₁); 1.31(d, 6H, ³J=6.1 Hz, H₁)

Synthesis of the Ruthenium Complex 1f

The N,N′-bis(4-isopropoxy-3-vinylphenyl)oxamide ligand 6f (8 mg; 0.02mmol; 1 eq.), copper chloride (I) (4 mg, 2.1 eq) and the indenylideneprecatalyst (37 mg, 2.1 eq.) are introduced into a round-bottom flaskunder argon. Anhydrous dichloromethane (5 mL) is added to it. Thereaction medium is then degassed three times, placed at 30-33° C. underan argon vacuum and kept under agitation for around 5 hours.

The raw reaction material is then concentrated under vacuum. The residueis combined with acetone (2 mL) and filtered on frit. The complex 1f isthus isolated in the form of a green solid (15 mg; 59%).

NMR ¹H (400 MHz, CD₂Cl₂) δ (ppm): 16.36 (s, 2H, H₉); 9.30 (s, 2H, NH);7.89 (d, 2H, ³J=7.8 Hz, H₅); 7.35 (s, 2H, H₇); 7.09 (s, 8H, H₁₂); 6.84(d, 2H, ³J=8.0 Hz, H₄); 4.86 (m, 2H, H₂); 4.16 (5, 8H, H₁₀); 1.86 (m,36H, H₁₁, H₁₃); 1.23 (d, 12H, ³J=6.1 Hz, H₁)

Synthesis of the Marked Ruthenium Complex 11

Once the trifluoroacetamide function is clearly identified as thefunction most capable of activating the precatalyst, the introduction ofan ion pattern (ion tag) can then be performed.

For this, the invention proposes substituting the chlorine atom ofcompound 10a with a tertiary amine (imidazole, pyridine, etc.).

Thus, the inventors performed the substitution with pyridine on4-chloro-N-(4-isopropoxy-3-vinylphenyl)butanamide 10a in order to easilyproduce the desired ion ligand 10b. The complexing thereof with theGrubbs II catalyst leads to complex 11.

Synthesis of the 4-chloro-N-(4-isopropoxy-3-vinylphenyl)butanamidecompound 10a

Using the general procedure for obtaining amides from4-isopropoxy-3-vinylaniline 5 (50 mg; 0.3 mmol) and with3-chloropropanoyl chloride (15 μL), acetamide is obtained afterchromatography on silica gel (eluent: CH₂Cl₂) in the form of a pinksolid (52 mg, 65%).

Rf (CH₂Cl₂)=0.3

NMR ¹H (400 MHz, CDCl₃) δ (ppm): 7.81 (s, 1H, NH); 7.54 (d, 1H, ⁴J=2.7Hz, H₇); 7.34 (dd, 1H, ³J=8.8 Hz, ⁴J=2.7 Hz, H₅); 6.98 (dd, 1H,³J_(cis)=11.2 Hz, ³J_(trans)=17.8 Hz, H₉); 6.79 (d, 1H, ³J=8.8 Hz, H₄);5.67 (dd, 1H, ²J_(gem)=1.4 Hz, ³J_(trans)=17.8 Hz, H_(10a)); 5.21 (dd,1H, ²J_(gem)=1.4 Hz, ³J_(cis)=11.2 Hz, H_(10b)); 4.44 (sept., 1H, ³J=6.1Hz, H₂); 3.60 (t, 2H, ³J=7.1 Hz, CH₂Cl); 2.48 (t, 2H, ³J=7.1 Hz, H₁₂);2.14 (m, 2H, H₁₁); 1.31 (d, 6H, ³J=6.1 Hz, H₁)

NMR ¹³C (100 MHz, CDCl₃) δ (ppm): 170.1 (C═O); 152.0 (C3); 131.3 (C9);130.8 (C8); 128.3 (C6); 121.1 (C7); 118.6 (C5); 115.0 (C4); 114.5 (C10);71.4 (C2); 44.4 (C13); 33.8 (C12); 27.9 (C11); 22.0 (Cl)

Synthesis of the1-(4-(4-isopropoxy-3-vinylphenylamino)-4-oxobutyl)pyridiniumhexafluorophosphate(V) compound 10b

Pyridine (1 mL) is added to an acetamide solution 10a (52 mg, 0.19 mmol)in anhydrous toluene, then the mixture is brought to reflux underagitation for 2 days. After evaporation of the solvent, the residue isdissolved in water, then KPF₆ (38 mg) is added. After 2 hours ofagitation at room temperature, the aqueous phase is extracted usingdichloromethane, then the organic phases are washed with a saturatedNaCl solution and dried on magnesium sulfate. After evaporation of thesolvent, the pyridinium salt is purified by chromatography on silica gel(eluent: CH₂Cl₂/MeOH (4:1)) in the form of an amorphous solid (38 mg,44%).

Rf (CH₂Cl₂/MeOH (8:2))=0.2

NMR ¹H (400 MHz, MeOD) δ (ppm): 8.98 (d, 2H, ³J=Hz, H₁₄); 8.54 (dd, 1H,³J=Hz, H₁₆); 8.06 (t, 2H, ³J=Hz, H₁₅); 7.62 (d, 1H, ⁴J=2.7 Hz, H₇); 7.30(dd, 1H, ³J=8.8 Hz, ⁴J=2.7 Hz, H₅); 6.97 (dd, 1H, ³J_(cis)=11.2 Hz,³J_(trans)=17.8 Hz, H₉); 6.88 (d, 1H, ³J=8.8 Hz, H₄); 5.70 (dd, 1H,²J_(gem)=1.4 Hz, ³J_(trans)=17.8 Hz, H_(10a)); 5.20 (dd, 1H,²J_(gem)=1.4 Hz, ³J_(cis)=11.2 Hz, H_(10b)); 4.69 (t, 2H, ³J=7.1 Hz,CH₂Pyr); 4.57 (s, 1H, NH); 4.50 (sept., 1H, ³J=6.1 Hz, H₂); 2.50 (t, 2H,³J=7.1 Hz, H₁₂); 2.38 (m, 2H, H₁₁); 1.31 (d, 6H, ³J=6.1 Hz, H₁)

NMR ¹³C (100 MHz, CDCl₃) δ (ppm): 171.9 (C═O); 153.2 (C3); 147.0 (C14);146.0 (C16); 132.8; 132.7; 129.5; 129.3; 122.4; 119.58; 116.2; 114.6;72.5; 62.5; 33.4; 27.9; 22.4

Synthesis of the Ruthenium Complex 11

The 1-(4-(4-isopropoxy-3-vinylphenylamino)-4-oxobutyl)pyridiniumhexafluorophosphate(V) ligand 10b (5 mg; 0.011 mmol; 1 eq.), copperchloride (I) (2 mg, 1 eq.) and the indenylidene precatalyst (9.6 mg, 1eq.) are introduced into a round-bottom flask under argon. Anhydrousdichloromethane (3 mL) is added to it. The reaction medium is thendegassed three times, placed at 30-33° C. under an argon atmosphere andkept under agitation for around 5 hours.

The raw reaction material is then concentrated under vacuum. The residueis combined with acetone (2 mL) and filtered on frit. The complex 11 isthus isolated in the form of an amorphous dark green solid.

NMR ¹H (400 MHz, (CD₃)₂CO) δ (ppm): 16.40 (s, 1H, H₉); 9.25 (d, 2H,³J=5.8 Hz, H₁₇); 9.18 (s, 2H, NH); 8.76 (t, 1H, ³J=6.5 Hz, H₁₉); 8.32(d, 2H, ³J=6.5 Hz, H₁₈); 7.62 (m, 2H, H₅); 7.50 (d, 1H, ³J=2.5 Hz, H₇);7.06 (s, 4H, H₁₂); 6.94 (d, 1H, ³J=8.8 Hz, H₄); 5.00 (t, 2H, ³J=7.1 Hz,H₁₈); 4.90 (m, 1H, H₂); 4.27 (s, 4H, H₁₀); 2.59 (m, 4H, H₁₄, H₁₈); 2.44(m, 18H, H₁₁ H₁₃); 1.23 (d, 6H, ³J=6.1 Hz, H₁)

In the second part, the activation of the activated ruthenium complexes1a, 1b, 1c, 1d, 1e and 1f was studied.

Complexes 1a, 1b, 1c, 1d according to the invention and the Hoveydacomplex 3b of the prior art were studied in an olefin cyclizationmetathesis reaction with diethylmalonate metallyl-allyl 7 at roomtemperature in dichloromethane in the presence of 1 mol % of complexaccording to the following reaction diagram.

The results of the conversion rates obtained with these compounds areshown in the graph of FIG. 1.

These results clearly show the acetamide function activating effect.

In particular, when this acetamide function has a trifluoromethyl group(complex 1b), a conversion rate of over 37% after only 15 minutes ofreaction is obtained, by comparison with 5% in the case of the Hoveydacomplex 3b.

The activity of compound 1e (resulting from the complexing with theNolan catalyst 2c) and of compound 1b (resulting from the complexingwith the Grubbs II catalyst 2b), on one hand, and that of the complex ofthe Hoveyda prior art complex 3b, on the other hand, were also studiedin the same reaction and under the same reaction conditions.

The results of the conversion rates obtained with these compounds areshown in the graph according to FIG. 2.

Very surprisingly, these results show a similar activity for catalysts1e and 1b, whereas the Grubbs complex II 2b (bearing a SIMes ligand) ismuch more active than the Nolan complex 2c (bearing an IMes ligand).This result is very beneficial because the catalytic species bearing anIMes ligand (resulting from the Nolan complex 2c) is much morethermically stable than the catalytic species bearing a SIMes ligand(generated by the Grubbs II complex 2b).

The invention therefore offers the possibility of performing olefinmetathesis reactions under more drastic conditions (higher heat) withthe activated complex 1e when the substrates are very bulky (for exampletetrasubstituted olefins). Thus a metathesis cyclization reaction of ametallyl-allyl diethyl malonate compound takes place at 45° C., in thepresence of 1 mol % of the catalytic complex 1e on one hand and at 30°C. in the presence of 1 mol % of the catalytic complexes 1b and 1e onthe other hand. The results of the conversion rates obtained with thesecompounds are shown in the graph according to FIG. 3. As expected, theactivated IMes catalyst 1e shows a remarkable activity with a conversionrate of 87% after only 6 minutes of reaction.

The activity of the activated complex 1b, by reducing its catalytic loadin the metathesis cyclization reaction of a metallyl-allyl diethylmalonate compound was also evaluated. FIG. 4 is a graph showing theconversion rate over time of a metallyl-allyl diethyl malonate in thecontext of a metathesis cyclization reaction at 30° C., in the presenceof 1 mol % of the catalytic complex according to the invention 1b and0.3 mol % of the catalytic complex according to the invention 1b. Thegraph shows a slight decrease in reactivity; however, it remainsremarkable since 75% of the conversion is observed after only 40 minutesof reaction.

Finally, the activated dimer complex 1f was also evaluated and itsactivity was compared with the activated complexes 1b and 1e. FIG. 5 isa graph showing the conversion rate over time of a metallyl-allyldiethylmalonate compound in the context of a metathesis cyclizationreaction at 30° C., in the presence of 1 mol % of the catalyticcomplexes according to the invention 1b, 1e and 1f.

What is claimed is:
 1. A compound of formula (I) for catalysis:

in which: L is a neutral ligand; X, X′ are anionic ligands; R¹ and R²are, independently, a hydrogen, a C₁ to C₆ alkyl, a C₁ to C₆perhalogenoalkyl, an aldehyde, a ketone, an ester, an amide, a nitrile,an optionally substituted aryl, a pyridinium alkyl, a pyridiniumperhalogenoalkyl or an optionally substituted C₅ or C₆ cyclohexyl, aC_(n)H_(2n)Y or C_(n)F_(2n)Y radical with n being between 1 and 6 and Ybeing an ion marker, or a radical of formula:

R² can also be hydrogen or a C₁ to C₆ alkyl; R¹ can be a radical offormula (I bis) when the compound is formula I:

R³ is a C₁ to C₆ alkyl or a C₅ or C₆ cycloalkyl or a C₅ or C₆ aryl; R⁴,R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹ are, independently, hydrogen, a C₁ to C₆alkyl, a C₁ to C₆ perhalogenoalkyl, or a C₅ or C₆ aryl; R⁹, R¹⁰, R¹¹ canform a heterocycle; X¹ is an anion selected from the group consisting ofhalogen, tetrafluoroborate ([BF₄]⁻),[tetrakis-(3,5-bis-(trifluoromethyl)-phenyl)borate] ([BARF]⁻),hexafluorophosphate ([PF₆]⁻), hexafluorantimonate ([SbF₆]⁻),hexafluoroarsenate ([AsF₆]⁻), and trifluoromethylsulfonate ([(CF₃)₂N]⁻);R¹ and R² can form with the N and the C to which they are attached aheterocycle of formula:

wherein hal is an halogen and R¹² is hydrogen, a C₁ to C₆ alkyl, or a C₅or C₆ cycloalkyl or a C₅ or C₆ aryl.
 2. Compound according to claim 1,wherein L is P(R¹³)₃, with R¹³ being a C₁ to C₆ alkyl or an aryl or a C₅or C₆ cycloalkyl.
 3. Compound according to claim 1, wherein L is aligand of formula 7a, 7b, 7c, 7d or 7e

in which: n¹=0, 1, 2, 3; R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸, R¹⁹, R²⁰, R²¹, R²²,R²³, R²⁴, R²⁵, R²⁶, R²⁷, R²⁸ are independently a C₁ to C₆ alkyl, a C₃ toC₂₀ cycloalkyl, a C₂ to C₂₀ alkenyl, a naphthyl, an anthracene or aphenyl, wherein said phenyl can be substituted by up to 5 groups chosenfrom the C₁ to C₆ alkyls, the C₁ to C₆ alkoxys and the halogens; R¹⁶ andR¹⁷, and R²⁶ and R²⁷ can form a cycle with 3, 4, 5, 6, or 7 links; R²⁸can independently form an aromatic cycle with 6 conjoined links. 4.Compound according to claim 1, wherein L is PCy₃, with Cy beingcyclohexyl, or L is a ligand of formula 7a or 7b, X is a chlorine, X′ isa chlorine.
 5. Compound according to claim 2, wherein the ion marker Yis selected from the group consisting of:


6. Compound according to claim 4, wherein R¹ is selected from the groupconsisting of CF₃, C₆F₅, and pNO₂C₆H₄.
 7. Compound according to claim 6,wherein in(I) R¹ is CF₃.
 8. Compound according to claim 4, whereinformula 1 is formula 1b:


9. Compound according to claim 4, wherein formula 1 is formula 1c:


10. Compound according to claim 4, wherein formula 1 is formula 1d:


11. Compound according to claim 4, wherein formula 1 is formula 1e:


12. Compound according to claim 4, wherein formula 1 is formula 1f:


13. Compound according to claim 4, wherein formula 1 is formula 1g:


14. Compound according to claim 4, wherein formula 1 is formula 1h:


15. Compound according to claim 4, wherein formula 1 is formula 1i:


16. Compound according to claim 4, wherein formula 1 is formula 1j:


17. Compound according to claim 4, wherein formula 1 is formula 1k:


18. Compound according to claim 4, wherein formula 1 is formula 11:


19. Compound according to claim 4, wherein formula 1 is formula 12:


20. Compound according to claim 4, wherein formula 1 is formula 13:


21. Compound according to claim 4, wherein formula 1 is formula 14:


22. Method for synthesis of a compound according to claim 1, comprisinga first step consisting of reacting 4-isopropoxy-3-vinylaniline with acompound having an acyl function so as to obtain an amide ligand and asecond step consisting of reacting said amide ligand with a compound offormula (III):


23. Method according to claim 22, wherein said compound of formula (III)is the Grubbs precatalyst (2b) or the Nolan precatalyst (2c).